Safety and Efficacy of Oral Fampridine-Sustained Release (SR) for the Treatment of Spasticity Resulting From Spinal Cord Injury

Spinal Cord Injury Clinical Trial

Official title:

Double-Blind, Placebo-Controlled, 12-Week Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR in Subjects With Moderate to Severe Spasticity Resulting From Chronic, Incomplete Spinal Cord Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01683838
• Other study ID #: SCI-F302
• Status: Completed
• Phase: Phase 3
• First received: August 24, 2012
• Last updated: January 6, 2014
• Start date: June 2002
• Est. completion date: February 2004

Study information

• Verified date: January 2014
• Source: Acorda Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Normally, nerve fibers carry electrical impulses through the spinal cord, providing communication between the brain and the arms and legs. In people with spinal cord injury, some fibers may be destroyed at the site of injury, while others remain connected but do not work correctly to carry electrical impulses. As a result, subjects with an incomplete spinal cord injury may have spasticity which is muscle spasms or muscle stiffness that makes movement difficult. Fampridine-SR is an experimental drug that increases the ability of the nerve to conduct electrical impulses. This study will examine the effects of Fampridine-SR on moderate to severe lower-limb spasticity, as well as the effects on bodily functions such as bladder control, bowel function and sexual function. The study will also examine the possible risks of taking Fampridine-SR.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: February 2004
• Est. primary completion date: November 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Incomplete traumatic Spinal Cord Injury (at least 18 months prior and stable for 6 months)

• Moderate to severe lower-limb spasticity

• Able to give informed consent and willing to comply with protocol

Exclusion Criteria:

• Pregnancy

• History of seizures

• Existing or history of frequent Urinary Tract Infections

• History of drug or alcohol abuse

• Allergy to pyridine-containing substances

• Received a botox injection 4 months prior to study

• Received an investigational drug within 30 days

• Previously treated with 4-aminopyridine (4-AP)

• Not on stable medication dosing in 3 weeks prior to study

• Abnormal ECG or laboratory value at screening

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Muscle Spasticity
• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Drug:
• Fampridine-SR
25mg bid (twice daily)
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	Chedoke-McMaster Hospital	Hamilton	Ontario
Canada	St. Mary's of the Lake Hospital	Kingston	Ontario
Canada	Health Sciences Centre	Winnipeg	Manitoba
United States	University of Michigan	Ann Arbor	Michigan
United States	UAB School of Medicine, 190 Spain Rehab Center	Birmingham	Alabama
United States	Boston University Medical Center	Boston	Massachusetts
United States	Charlotte Institute of Rehabilitation	Charlotte	North Carolina
United States	University of Missouri	Columbia	Missouri
United States	Ohio State University	Columbus	Ohio
United States	Southwestern Medical Center at Dallas	Dallas	Texas
United States	VA North Texas Health Care System	Dallas	Texas
United States	Miami Valley Hospital- Rehabilitation Institute of Medicine	Dayton	Ohio
United States	Rehabilitation Institute of Michigan	Detroit	Michigan
United States	Craig Hospital	Englewood	Colorado
United States	INOVA Institute of Research and Education	Falls Church	Virginia
United States	Hines VA Hospital	Hines	Illinois
United States	Long Beach VA Medical Center	Long Beach	California
United States	Wood VA Medical Center	Milwaukee	Wisconsin
United States	Minneapolis VA Hospital	Minneapolis	Minnesota
United States	Hospital for Special Care	New Britain	Connecticut
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Medical College of Virginia/VCU	Richmond	Virginia
United States	University of Rochester/Strong Memorial Hospital	Rochester	New York
United States	University of California, Davis	Sacramento	California
United States	Santa Clara Valley Medical Center	San Jose	California
United States	University of Washington Medical Center, Dept. of Rehabilitation	Seattle	Washington
United States	St. Louis University	St. Louis	Missouri
United States	SUNY Upstate Clinical Trials Office	Syracuse	New York
United States	Helen Hayes Hospital	West Haverstraw	New York
United States	Coastal AHEC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Acorda Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity	The Ashworth evaluates the functioning of two lower extremity muscle groups, the hamstring and quadriceps muscles, while in the supine position. The test measures extension of the right and left hamstring muscle and flexion of the right and left quadriceps muscle using the following 5-point grading scale: 1=no increased tone; 2=slight increase in tone, giving a "catch" when the affected part is moved in flexion or extension; 3=more marked increase in tone, but affected part is easily flexed; 4=considerable increase in tone, passive movement is difficult; 5=affected part is rigid in flexion and extension.; The Ashworth Score was determined by adding all individual scores for each muscle group and dividing by four. Higher Ashworth Scores indicated greater spasticity.	Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98	No
Primary	Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores	The SGI is a 7-unit ordinal scale used by the subject to evaluate the effects of study medication on his/her quality of life during the preceding week, with higher scores denoting greater satisfaction. A positive change score in SGI signifies improved outcome.; The questionnaire consisted of one question (How do you feel about the effects of the investigational drug over the past 7 days?). The answer was based on a numerical rating scale where 1=terrible; 2=unhappy; 3=mostly dissatisfied; 4=neutral/mixed; 5=mostly satisfied; 6=pleased; 7=delighted.	Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98	No
Secondary	Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores	The Spasm Frequency score is the average rating by the clinician of the left and right arm(s) and leg(s), each evaluated on a 4-point scale (from 0=no spasms to 4=spontaneous spasms occurring more than ten times per hour), with higher scores denoting a greater degree of muscle spasms.; The Spasm Severity score is the average rating of the left and right arm(s) and leg(s), each evaluated on a three-point scale (mild, moderate, or severe) as rated by the clinician on the basis of patient self-report.; On both, a negative change in score signifies improvement in muscle spasms. The average Spasm Frequency/Spasm Severity Score was calculated as the average of the left and right non-missing scores.	Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98	No
Secondary	Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores	The supervising clinician rated the patient's neurological condition following treatment as compared to the screening visit on a seven-point scale (from 1=very much improved to 7=very much worse). The assessment was based on the clinician's overall impression of the patient's neurological status (specifically bowel, bladder, and sexual function; spasticity; and other neurological functions) and general state of health related to his or her participation in the study. Negative change scores indicated a change for the better.	Baseline (visits 2,3) average of days 7-14 and double-blind treatment period (visits 4-7) average of days 28-98)	No
Secondary	Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score	Ten key muscle groups for the right and left sides were rated on a 0 (absent) to 5 (normal) scale, with a possible total score of 100. Higher positive change scores indicate improved motor function.	Baseline (visits 2,3) average score days 7,14 and stable-dose treatment period (visits 5-7) average score days 56-98	No
Secondary	Change From Baseline in Mean International Index of Erectile Function (IIEF) Score	Male patients were asked to complete the IIEF questionnaire on sexual function. The IIEF is a brief, reliable, and valid self-administered questionnaire of 15 questions (items) that were categorized into five domains: Erectile Function (EF) scores: 0-6 Severe dysfunction, 7-12 Moderate dysfunction, 13-18 Mild to moderate dysfunction, 19-24 Mild dysfunction, 25-30 No dysfunction. Orgasmic Function (OF) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Sexual Desire (SD) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Intercourse Satisfaction (IS) score range: 0-3 Severe dysfunction to 13-15 No dysfunction, and Overall Satisfaction (OS) score range: 0-2 Severe dysfunction to 9-10 No dysfunction.; Domain scores were derived by summing the individual items within a given domain. Final scale ranges from 0 (negative) to 5 (positive). A positive change in IIEF domain scores signifies improvement.	Baseline (visit 1) average score obtained at day 1 and stable treatment period (visit 7) average score day 98	No
Secondary	Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores	The FSFI is a brief, reliable, and valid self-administered questionnaire of 19 questions (items). It contains six domains: Desire (2 items score range: 1 Very low or none at all to 5 Very high), Arousal (4 items score range: 0 No sexual activity to 5 Almost always or always), Lubrication (4 items score range: 0 No sexual activity to 5 Almost always or always), Orgasm (3 items score range: 0 No sexual activity to 5 Almost always or always), Satisfaction (3 items score range: 0 No sexual activity to 5 Very satisfied) and Pain (3 items score range: 0 Did not attempt intercourse to 5 Almost never or never).; A positive change signifies improvement.	Baseline (visit 1) average score obtained at day 1 and stable treatment period (visits 4-7) average score days 28-98	No
Secondary	Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores	Bowel/bladder questions pertaining to the average number of times per day the patient experienced accidental urination/leakage and the average number of bowel movements per day were asked of all patients daily.; A negative change in patient bladder/bowel function diary score signifies improvement.	Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98	No
Secondary	Adjusted Mean Change in Subject Bowel Function Diary Scores	Bowel questions pertaining to the average number of minutes per day spent on bowel routine were asked of all patients daily.; A negative change in patient bowel function diary score signifies improvement.	Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98	No

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